About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesFollowing myocardial infarction, the prognosis for females is better than males. Estrogen is thought to be protective, but clinical trials with hormone replacement failed to show protection. Here, we sought to identify novel mechanisms that might explain this sex-based difference. By diverging from the traditional focus on sex hormones, we employed a conceptually novel approach to this question by using a non-biased approach to measure global changes in gene expression following infarction.
An association between gene expression and better survival in female mice following myocardial infarction.
Sex, Specimen part
View SamplesTo evaluate and characterize gene expression changes and toxicity following oral gavage administration of AMG A & AMG B in male Sprague Dawley rats.
Application of genomics for identification of systemic toxicity triggers associated with VEGF-R inhibitors.
No sample metadata fields
View Samples-chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of neoprene elastomers, is of regulatory interest due to the production of multi-organ tumors in mouse and rat cancer bioassays. A significant increase in female mouse lung tumors was observed at the lowest exposure concentration of 12.8 ppm while a small, but not statistically significant, increase was observed in female rats only at the highest exposure concentration of 80 ppm. The metabolism of chloroprene results in the generation of reactive epoxides and the rate of overall chloroprene metabolism is highly species dependent. To identify potential key events in the mode-of-action of chloroprene lung tumorigenesis, dose response and time course gene expression microarray measurements were made in the lungs of female mice and female rats. The gene expression changes were analyzed using both a traditional analysis of variance approach followed by pathway enrichment analysis and a pathway-based benchmark dose (BMD) analysis approach. Pathways related to glutathione biosynthesis and metabolism were the primary pathways consistent with cross-species differences in tumor incidence and transcriptional BMD values for the pathway were more similar to differences in tumor response than were estimated target tissue dose surrogates based on the total amount of chloroprene metabolized per unit mass of lung tissue per day. The closer correspondence of the transcriptional changes with the tumor response are likely due to their reflection of the overall balance between metabolic activation and detoxication reactions whereas the current tissue dose surrogate reflects only oxidative metabolism.
Cross-species transcriptomic analysis of mouse and rat lung exposed to chloroprene.
Sex, Age, Specimen part, Subject
View SamplesEnhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF- signaling, and inflammatory pathway. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, Notch Signaling Pathway, natural killer cell mediated cytotoxicity, and B cell receptor signaling pathway, among others. The decreased group exclusively consists of genes involved in heme biosynthesis, p53 signaling pathway, and hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified.
Temporal gene expression profiling during rat femoral marrow ablation-induced intramembranous bone regeneration.
Sex, Specimen part, Time
View SamplesMicroarrays have been widely used for the analysis of gene expression and several commercial platforms are available. The combined use of multiple platforms can overcome the inherent biases of each approach, and may represent an alternative that is complementary to RT-PCR for identification of the more robust changes in gene expression profiles.
Cross platform microarray analysis for robust identification of differentially expressed genes.
No sample metadata fields
View SamplesTreatment with Aurora inhibitors has been shown to induce diverse biological responses in different tumor cell lines, in part depending on their p53 status. To characterize at the transcriptional level the effects of Danusertib we analyzed by microarray different tumor cell lines, with WT or mutant p53 status, that showed differential cell cycle response upon drug treatment.
Transcriptional analysis of the Aurora inhibitor Danusertib leading to biomarker identification in TP53 wild type cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesMyeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or polarization and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS).
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesMyeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or polarization and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS).
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View Samples